A 74-year-old woman came to this clinic with complaints of discomfort in the perineal region for the past 20 days. She said that she had noticed hardening in a small area, which she had ignored for the past few months, but she had experienced some burning during passing urine and stool. On examination there was small, well-defined erosion on her perineum [Figure 1]. There was no bleeding, pruritus, pus discharge, or tenderness. There was no palpable mass. She was a well-controlled diabetic. A potassium hydroxide (KOH) and Gram-stain smear did not reveal any abnormality. Owing to its essentially asymptomatic nature, long duration, and the pigmentation around it, we considered a differential diagnosis of pigmented basal cell carcinoma, malignant melanoma, and pigmented Bowen's disease. A skin biopsy revealed large intraepithelial cells, with a pale staining cytoplasm and large pale staining nuclei [Figure 2] and [Figure 3]. The immunohistochemistry was positive for cytokeratin 7 (CK7), but was negative for cytokeratin 20 (CK20), S 100, and β-Hydroxy β-methylbutyric acid (HMB) 45 [Figure 4]. Serum carcinoembryonic antigen (CEA) was normal. A Papanicolaou (PAP) smear, pelvic X-ray, pelvic ultrasound, a gynecologic examination, and colonoscopy did not reveal anything abnormal. Integrating the results of the clinical findings, routine histology and immunohistochemistry, a diagnosis of XXX was made.

Figure 2: Markedly hyperplastic epidermis with 'bulbous' ridges proliferating downward. The cells near the basal epithelium are rather pale and sharply delineated from the dermis by a basal layer of the epidermis. (H and E, ×10)

Extramammary Paget's disease is a rare malignancy. [1],[2],[3] It is seen in ages between 50 and 80 years, has a female preponderance, and is unusual in patients with dark skin. [1],[3] It commonly affects areas rich in apocrine glands, with a predominance of lesions on the vulva and perineum, but has been rarely reported in the axillae, buttocks, eyelids, thighs, or the external auditory canal. [1] It is usually a slow enlarging plaque that may mimic eczema, psoriasis, lichen simplex chronicus, basal cell carcinoma, pigmented Bowen's disease, or malignant melanoma. [2],[3],[4] Itching is the most common symptom. The characteristic features are the same as mammary Paget's disease, with the intraepithelial mucus secreting Paget cells with abundant cytoplasm and abnormally large nuclei. It usually stains positive for colloidal iron, Alcian blue, mucicarmine E, and Periodic acid-Schiff (PAS) stains. There are three forms described with the most commonly occurring primary one, which is the pure intraepithelial form (31-42%). [2] The secondary forms can be either associated with adnexal malignancies or visceral malignancies, which are usually adenocarcinomas of the gastrointestinal or genitourinary tract. In addition, the intraepidermal Paget cells can themselves descend into the dermis and metastasize. [3] The mortality in the latter is said to be 46% higher, which may be because the disease mimics so many benign conditions, resulting in the delay of diagnosis and treatment of the underlying malignancy. [2]

In this case the positive CK7 confirmed the apocrine origin of Paget's disease, which was diagnosed by routine histology. Negative S100 and HMB 45 ruled out malignant melanoma. Negative CK20 and carcinoembryonic antigen (CEA) aided the clinical procedures performed to rule out frequently associated visceral malignancies. The genitalia and perineal area are always relatively more pigmented in the South Asian population, and therefore, may pose diagnostic challenges in such unusual diseases. A pigmented EMPD has also been described, where the pigment is seen in the Paget cells and there is a presence of dendritic melanocytes.

Its insidious nature and nonspecific clinical features often delay the diagnosis of extramammary Paget's disease by five-to-ten years, and therefore, it is prudent to consider it an extensive lesion and do a wide excision. [2],[5] Other treatments that have been used, include topical 5-fluorouracil, bleomycin, Imiquimod, radiation, and oncosurgical intervention in case of underlying carcinoma. [2],[3],[5]